Wireless, Multi-Sensor System-on-Chip for pH and Amperometry Powered by Body Heat.

This article presents a body-heat-powered, multi-sensor SoC for measurement of chemical and biological sensors. Our approach combines analog front-end sensor interfaces for voltage- (V-to-I) and current-mode (potentiostat) sensors with a relaxation oscillator (RxO) readout scheme targeting << 10 µW power consumption. The design was implemented as a complete sensor readout system-on-chip, including a low-voltage energy harvester compatible with thermoelectric generation and a near-field wireless transmitter. A prototype IC was fabricated in a 0.18 µm CMOS process as a proof-of-concept. As measured, full-range pH measurement consumes 2.2 µW at maximum, where the RxO consumes 0.7 µW and measured linearity of the readout circuit demonstrates R 2 0.999. Glucose measurement is also demonstrated using an on-chip potentiostat circuit as the input of the RxO, with a readout power consumption as low as 1.4 µ W. As a final proof-of-principle, both pH and glucose measurement are demonstrated while powering from body heat using a centimeter-scale thermoelectric generator on the skin surface, and pH measurement is further demonstrated with an on-chip transmitter for wireless data transmission. Long-term, the presented approach may enable a variety of biological, electrochemical, and physical sensor readout schemes with microwatt operation for batteryless and power autonomous sensor systems.

A Reconfigurable Tri-Mode Frequency-Locked Loop Readout Circuit for Biosensor Interfaces.

In this article, a frequency-locked loop (FLL) based multimodal readout integrated circuit (IC) for interfacing with off-chip temperature, electrochemical, and pH sensors is presented. By reconfiguring its switched-capacitor feedback network, the readout circuit is able to measure resistance, current, and voltage without additional active analog front-end circuits. A prototype IC was fabricated in a 0.18 µm CMOS process. Measured results show that when measuring resistance, the input-referred resistance resolution is 10.5 Ω for 100 Hz integration bandwidth. Using an off-chip thermistor, the readout circuit covers a temperature range of 0-75 °C and achieves an equivalent temperature resolution of 16.4 mKrms. In current mode, the readout circuit has an input range of 0.5µA and an input-referred current noise as low as 40.6 pArms for 100 Hz bandwidth. Interfacing with an on-chip potentiostat, glucose chronoamperometry is demonstrated. In voltage mode, a minimum input-referred voltage noise of 31.7 µVrms is achieved, and the IC can measure a pH range from 1.6 to 12 using a commercial pH probe. At a 1.2 V supply, power consumption of the readout circuit is below 10 µW for all three measurement modes. Additionally, the prototype IC includes an integrated wireless transmitter that implements on-off keying modulation, and a wireless multimodal sensing system utilizing the FLL-based readout circuit is demonstrated.

Eye Drop Adherence With an Eye Drop Bottle Cap Monitor.

PRCIS: An eye drop bottle cap monitor with audio and visual alarms measured eye drop adherence in 50 subjects with glaucoma. Baseline adherence rates were too high to test if the alarms could improve adherence. PURPOSE: To determine if an eye drop bottle cap monitor can measure and improve adherence. MATERIALS AND METHODS: The Devers Drop Device (D3, Universal Adherence LLC) was designed to measure eye drop adherence by detecting bottle cap removal and replacement, and it can provide text, visual and audio alerts when a medication is due. In Stage 1, we determined baseline adherence for 50 subjects using a nightly eye drop over a 25-day period. Subjects with less than 90% baseline adherence were eligible for Stage 2. In Stage 2, we randomized subjects to receive either no reminder or automated D3 alerts for their nightly eye drop over a subsequent 25-day period. We defined adherence as the proportion of drops administered within 3 hours of the subjects' scheduled dosing time. Subjects completed 3 questions regarding satisfaction with the device and willingness to pay. RESULTS: The D3 monitor remained attached to the eye drop bottle cap for the duration of the study and collected adherence data in all 50 patients. In Stage 1, the mean adherence rate was 90 ± 18% (range 32-100%). Forty (80%) subjects had an adherence rate greater than 90%. Adherence rates were too high in Stage 1 to adequately test the effects of reminders in Stage 2. Ninety-eight percent (49/50) and 96% (48/50) of subjects agreed "the device always stayed attached to the bottle cap" and "I was able to use the device to take the drops", respectively. Patients would pay $61±83 (range $0-400) for a similar device to improve adherence. CONCLUSIONS: The D3 can measure eye drop adherence. Research subjects reported high satisfaction and willingness to pay for an eye drop bottle cap monitor. Glaucoma patients have high adherence when they are being monitored, and future studies with research subjects screened for poor adherence may further determine the benefit of electronic monitoring of adherence with and without electronic reminders.

A 10 M Ω, 50 kHz-40 MHz Impedance Measurement Architecture for Source-Differential Flow Cytometry.

A low-power, impedance-based integrated circuit (IC) readout architecture is presented for cell analysis and cytometry applications. A three-electrode layout and source-differential excitation cancels baseline current prior to the sensor front-end, which enables the use of a high-gain readout circuit for the difference current. A lock-in architecture is employed with down-conversion and up-conversion in the feedback loop, enabling high closed-loop gain (up to 10 M Ω) and high bandwidth (up to 40 MHz). A hybrid-RC feedback network mitigates the SNR degradation seen over a wide operating frequency range when using purely capacitive feedback. The effect of phase shift on the closed-loop system gain and noise performance are analyzed in detail, along with optimization strategies, and the design includes fine-grained phase adjustment to minimize phase error. The impedance sensor was fabricated in a 0.18 µ m CMOS process and consumes 9.7 mW with an operating frequency from 50 kHz to 40 MHz and provides adjustable bandwidth. Measurements demonstrate that the impedance sensor achieves 6 pA [Formula: see text] input-referred noise over 200 Hz bandwidth at 0.5 MHz modulation frequency. Combined with a microfluidic flow cell, measured results using this source-differential measurement approach are presented using both monodisperse and polydisperse sample solutions and demonstrate single-cell resolution, detecting 3 µ m diameter particles in solution with 22 dB SNR.

A Passive Wideband Noise-Canceling Mixer-First Architecture With Shared Antenna Interface for Interferer-Tolerant Wake-Up Receivers and Low-Noise Primary Receivers.

Wake-up receivers (WuRX) present an opportunity to reduce average power consumption of IoT transceivers, however achieving sensitivity and interferer tolerance while providing wideband matching and sharing an antenna interface present a significant challenge for existing architectures. This paper presents a primary/WuRX which utilizes a quadrature hybrid coupler based N-Path mixer first architecture to simultaneously achieve low noise, wideband matching and a shared antenna interface. The passive-mixer first approach and a two-code modulated multi-tone signaling scheme provide interferer tolerance in the WuRX. The paper analyzes gain/power trade-offs in the proposed architecture in the context of noise impact with multi-tone WuRX signaling. The proposed architecture is implemented in 65 nm CMOS and occupies 2.25 mm 2. The primary RX achieves 3.8 dB NF and 0.75 dBm out-of-band P1dB with 440µW power consumption. The WuRX achieves -86 dBm sensitivity for 10kb/s data rate and up to -40 dB signal-to-interferer ratio (SIR) with 171µW power consumption.

Analysis of Skin-Worn Thermoelectric Generators for Body Heat Energy Harvesting to Power Wearable Devices.

The rapid growth of wearable electronic devices motivates investigation of powering such devices using energy harvesting, with the long-term goal of continuous operation without the need to recharge or replace batteries. In this work, we present a study conducted using a wearable device to measure the voltage, power, and energy that can be harvested continuously from human body heat using a thermoelectric generator (TEG) worn on the skin surface. Using a TEG worn on the arm, we demonstrate an average of 22.9 µW continuous maximum power delivery across three subjects, corresponding to 1.43 µW/cm2 power density. Additionally, the large thermal gradient across the TEG when first placed on the skin provides sufficient voltage output across a matched load to enable cold start of state-of-the-art DC-DC boost converters. Overall, the results demonstrate sufficient power density and voltage output provided by centimeter-scale TEGs for operating battery-less, wearable sensor devices using body heat energy harvesting.

Multi-Channel Biopotential Acquisition System Using Frequency-Division Multiplexing With Cable Motion Artifact Suppression.

A multi-channel, CMOS-based biopotential acquisition system is presented that uses amplitude modulated, frequency division multiplexing (AM-FDM) to decrease wire count and provide resilience against motion artifacts and cable noise. Differential active electrode (AE) pairs capture surface biopotential signals, each modulated by a different carrier frequency and combined via current-domain summing. The presented approach requires only a single wire for signal transmission between AEs and back-end readout, along with clock and ground wires, to support multiple active electrodes using a 3-wire cable. Frequency modulation prior to transmission mitigates the effect of low-frequency cable motion artifacts and 50/60 Hz mains interference in the cable. A prototype FDM-based biopotential acquisition system was implemented in a 180 nm CMOS process, including a four-channel front-end active electrode IC for signal conditioning and modulation, and a back-end IC for demodulation and digitization. Each channel occupies 0.75 mm [Formula: see text] and consumes 43.8 µ W, inclusive of ADC power. Using both AE and BE ICs, a four-channel biopotential recording system is demonstrated using a 3-wire interface, where the system achieves attenuation of low-frequency cable motion artifacts by 15X and 60 Hz mains noise coupled into the cable by 62X.

A 3.5 mV Input Single-Inductor Self-Starting Boost Converter with Loss-Aware MPPT for Efficient Autonomous Body-Heat Energy Harvesting.

A single-inductor self-starting boost converter is presented suitable for thermoelectric energy harvesting from human body heat. In order to extract maximum energy from a thermoelectric generator (TEG) at small temperature gradients, a loss-aware maximum power point tracking (MPPT) scheme was developed that enables the harvester to achieve high end-to-end efficiency at low input voltages. The boost converter is implemented in a 0.18 µm CMOS technology and is more than 75% efficient for a matched input voltage range of 15 mV-100 mV, with a peak efficiency of 82%. Enhanced power extraction enables the converter to sustain operation at an input voltage as low as 3.5 mV. In addition, the boost converter self-starts with a minimum TEG voltage of 50 mV leveraging a dual-path architecture without using additional off-chip components.

Frequency-Division Multiplexing with Graphene Active Electrodes for Neurosensor Applications.

Multielectrode arrays are used broadly for neural recording, both in vivo and for ex vivo cultured neurons. In most cases, recording sites are passive electrodes wired to external read-out circuitry, and the number of wires is at least equal to the number of recording sites. We present an approach to break the conventional N-wire, N-electrode array architecture using graphene active electrodes, which allow signal upconversion at the recording site and sharing of each interface wire among multiple active electrodes using frequency-division multiplexing (FDM). The presented work includes the design and implementation of a frequency modulation and readout architecture using graphene FET electrodes, a custom integrated circuit (IC) analog front-end (AFE), and digital demodulation. The AFE was fabricated in 0.18 µm CMOS; electrical characterization and multi-channel FDM results are provided, including GFET-based signal modulation and IC/DSP demodulation. Long-term, this approach can simultaneously enable high signal count, high spatial resolution, and high temporal precision to infer functional interactions between neurons while markedly decreasing access wires.

A Batteryless Motion-Adaptive Heartbeat Detection System-on-Chip Powered by Human Body Heat.

This paper presents a batteryless heartbeat detection system-on-chip (SoC) powered by human body heat. An adaptive threshold generation architecture using pulse-width locked loop (PWLL) is developed to detect heartbeats from electrocardiogram (ECG) in the presence of motion artifacts. The sensing system is autonomously powered by harvesting thermal energy from human body heat using a thermoelectric generator (TEG) coupled to a low-voltage, self-starting boost converter and integrated power management system. The SoC was implemented in a 0.18 µm CMOS process and is fully functional with a minimum input power of 20 µW, provided by a portable TEG at 20 mV with a ~0.5 °C temperature gradient. The complete system demonstrates motion-adaptive, power-autonomous heartbeat detection for sustainable healthcare using wearable devices.

A 6-Transistor Ultra-Low Power CMOS Voltage Reference with 0.02%/V Line Sensitivity.

This work presents a technique for design of ultra-low power (ULP) CMOS voltage references achieving extremely low line sensitivity while maintaining state-of-the-art temperature insensitivity through the use of a 6-transistor (6T) structure. The proposed technique demonstrates good performance in sub-100 nm CMOS technologies. The 65-nm CMOS implementation occupies only 840 µm2 of area and consumes 28.6 pA from a 0.5 V supply. Measurements from 6 samples from the same wafer show an average line sensitivity of 0.02 %/V, a 10X improvement over previous 65 nm implementations, and an average temperature coefficient of 99.2 ppm/°C.

DC-100 kHz Tunable Readout IC for Impedance Spectroscopy and Amperometric Measurement of Electrochemical Sensors.

This paper presents a low-noise, front-end sensor IC that includes both AC impedance spectroscopy and DC amperometric measurement capabilities for electrochemical and biosensor applications. A common-gate current buffer topology is proposed that supports both current-mode and voltage-mode sensor signals to allow an input frequency range from DC to 100 kHz. Low-noise operation is achieved across a wide input frequency range using tunable high-pass and low-pass frequency response. In addition, an incremental delta-sigma modulator with embedded frequency response analysis serves as both on-chip impedance analyzer and current-driven analog-to-digital converter. Implemented using a 0.18 µm CMOS process, this work achieves 45 fA/√Hz input current noise density at 1 kHz. Input dynamic range exceeding 80 dB is achieved up to 10 kHz bandwidth, with a maximum of 104 dB dynamic range at 10 Hz.

Integrated Cold-Start of a Boost Converter at 57mV using Cross-Coupled Complementary Charge Pumps and Ultra-Low-Voltage Ring Oscillator.

This paper demonstrates an on-chip electrical cold-start technique to achieve low-voltage and fast start up of a boost converter for autonomous thermal energy harvesting from human body heat. An improved charge transfer through high gate-boosted switches by means of cross-coupled complementary charge pumps enables voltage multiplication of the low input voltage during cold start. The start-up voltage multiplier operates with an on-chip clock generated by an ultra-low-voltage ring oscillator. The proposed cold-start scheme implemented in a general purpose 0.18µm CMOS process assists an inductive boost converter to start operation with a minimum input voltage of 57mV in 135 ms while consuming only 90 nJ of energy from the harvesting source, without using additional sources of energy or additional off-chip components.

Wireless Smartphone Control using Electromyography and Automated Gesture Recognition.

In this paper, a wearable, wireless system is demonstrated using electromyography (EMG) signals for realtime control of a smartphone device. The system allows gesturebased control of a smartphone or tablet computer without physical contact, direct line of sight, or significant movement. Additionally, automated gesture detection is shifted to the smartphone, eliminating the need for robust computing hardware. The electronic system and gesture prediction algorithm are described, and measured results are presented and for multiple users. The system demonstrates a maximum true positive detection rate of 92% for a trained user, using three distinct hand gestures. The EMG-based detection system serves as a proof-of-concept for providing wireless, gesture-based control of computer interfaces using low-cost consumer hardware.

Heterogeneous Integration of CMOS Sensors and Fluidic Networks Using Wafer-Level Molding.

Direct sensing in liquids using CMOS-integrated optical and electrical sensors is attractive for lab-on-chip applications, where close physical proximity between sample and sensor can obviate optical lenses, enhance electrical sensitivity, and decrease noise due to parasitics. However, controlled delivery of fluid samples to the chip surface presents an ongoing challenge for lab-on-CMOS development, where traditional wire-bond packaging prevents integration of planar microfluidics. In this paper, we present a method for scalable heterogeneous integration of microfluidic channels and silicon-integrated circuit substrates using a commercial fan-out wafer-level packaging approach. The planar surface supports multiple approaches for fluidic integration; we present both a stacked laser-cut fluidic assembly and the fabrication of monolithic SU-8 microchannels over the IC surface. As a proof-of-principle, both electrical and fluidic routing are provided to a custom 0.18-m CMOS optical sensor IC, and optical transmission and fluorescence measurement experiments are demonstrated.

Whole-blood immunoassay for γH2AX as a radiation biodosimetry assay with minimal sample preparation.

The current state of the art in high-throughput minimally invasive radiation biodosimetry involves the collection of samples in the field and analysis at a centralized facility. We have developed a simple biological immunoassay for radiation exposure that could extend this analysis out of the laboratory into the field. Such a forward placed assay would facilitate triage of a potentially exposed population. The phosphorylation and localization of the histone H2AX at double-stranded DNA breaks has already been proven to be an adequate surrogate assay for reporting DNA damage proportional to radiation dose. Here, we develop an assay for phosphorylated H2AX directed against minimally processed sample lysates. We conduct preliminary verification of H2AX phosphorylation using irradiated mouse embryo fibroblast cultures. Additional dosimetry is performed using human blood samples irradiated ex vivo. The assay reports H2AX phosphorylation in human blood samples in response to ionizing radiation over a range of 0-5 Gy in a linear fashion, without requiring filtering, enrichment, or purification of the blood sample.